Effect of CYP3A5 genotypes on serum carbamazepine concentrations at steady-state in Vietnamese epileptic patients
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This study aims to investigate whether CYP3A5 polymorphisms affect steady-state carbamazepine (CBZ) concentrations and therapeutic effects of CBZ monotherapy in Vietnamese epileptic patients.
A prospective study was conducted from December 2016 to June 2017 at Neurology Department at Nhan Dan Gia Dinh hospital, Vietnam. CBZ concentrations were measured using the fluorescence polarization immuno assay and CYP3A5 were genotyped using a polymerase chain reaction-restriction fragment length polymorphism.
Thirty-two patients were CYP3A5 expressors (twenty-three for CYP3A5 *1/*1 and nine for CYP3A5*1/*3) and six patients were CYP3A5 non-expressors (CYP3A5*3/*3). Dose normalized concentrations (mean ± SD) of CBZ were 7.9 ± 3.5 ng/mL/mg for CYP3A5 expressors and 8.1 ± 3.7 ng/mL/mg for CYP3A5 non-expressors. There was no statistically significant difference in efficacy between the two groups (χ2 = 0.17, p = 0.37). A positive correlation between dose requirement of CBZ and serum level of CBZ was observed in both the CYP3A5 expressors (r = 0.28, p = 0.11) and the CYP3A5 non-expressors (r = 0.03, p = 0.95). However, when the concentration of CBZ normalized by the CBZ doses administered, a negative correlation was observed in both CYP3A5 expressors (r = 0.5, p = 0.004) and CYP3A5 non-expressors (r = 0.5, p = 0.33).
The CYP3A5 genotype affected the CBZ concentrations in Vietnamese epileptic patients and is a factor that may contribute to the individual variability of CBZ efficacy in epileptic patients.
Therapeutic drug monitoring, genetic polymorphisms, CYP3A5, epilepsy, Vietnam.